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Block 1 > Week 6 Random > Flashcards

Week 6 Random Flashcards

1
Q

Which embyonic layer gives rise to the epihelium? connective tissue?

A

E: Ectoderm, Mesoderm, Endoderm

C: Mesoderm, Ectoderm (head)

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2
Q

Where is epithelium found?

A

It lines all cavities and outside surfaces.

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3
Q

What are the functions of epithelia?

A

Protection

Transcellular Transport (e.g. vessicles for IgA, carrier protein aa & glucose, and diffusion of oxygen in alveoli)

Secretion (exocytosis e.g. hormones)

Absorption (endocytosis e.g. PCT in kidney)

Selective Permeability

Sensory Organ (e.g. taste buds, retina, hair cells)

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4
Q

What is another name for intermediate filaments?

A

Cytokeratin / Tonofilaments

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5
Q

Characteristic of epithelium

A

Polarized

Intermediate Filaments

Connected by junctions that form sheets

Separated by basement membrane

Avascular

Rapid regeneration

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6
Q

Simple Squamous Epithelium

Location and Function

A

Pulmonary aveoli (gaseous exchange)

parietal layer of Bowman’s capsule (fluid exchange)

loop of Henle

inner and middle ear

Endothelium: blood and lympathic vessels (lubrication)

Mesothelium: pleural and peritoneal cavities (reducing friction)

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7
Q

Simple Cuboidal Epithelium

Location and Function

A

Ducts

Distal tubule in kidney (absorption)

Glands (secretion)

Surface of ovary (protection)

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8
Q

Simple Columnar Epithelium

Location and Example

A

Oviduct (transport)

Efferentes of testis (transport)

Uterus (secretion)

Small bronchi

Digestive tract (secretion/absorption)

Small gallbladder and excretory ducts in some glands (protection)

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9
Q

Simple Pseudostratified Epithelium

Location and Example

A

Trachea (secretion/absorption)

Primary bronchi

Epididymis and ductos deferens

Auditory tube (protection)

Tympanic cavity

Lacrimal Sac

Male urethra (transportaion/lubrication)

Large excretory duct

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10
Q

Two types of epithelium

A

Endothelium: lining of blood vessels and lympathics

Mesothelium: lining of body cavities

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11
Q

Simple vs. Stratified Epithelium

A

In simple epithelium, all cells lie upon the basement membrane.

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12
Q

Two types of stratified squamous epithelium

A

nonkeratinized stratified / moist (associated with mucosa) - have alive cells at the surface

keratinized - have denucleated cells at the surface

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13
Q

Stratified Squamous (non-keratinized) Epithelium

Location and Examples

A

Functions: protection & secretion

Examples: Mouth, Epiglottis, Escophagus, Vocal cords, and Vagina

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14
Q

Stratified Squamous (Keratinized) Epithelium

Location and Function

A

Epidermis of skin

Protection

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15
Q

Cuboidal Stratified Epithelium

Location and Function

A

Lining ducts of sweat glands

Absorption and secretion

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16
Q

Stratified Columnar Epithelium

A

Conjuctiva of eye, some large exretory ducts, portion of male urethra

Secretion, absorption, protection

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17
Q

Transitional Epithelium

A

Linig of urinary passages from renal calyces to the urethra

Protection and distensible

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18
Q

Functions of basement membrane

A

Anchoring

Vascular layer

Transcellular transport

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19
Q

What are microenviroments in epithelial cell?

A

Apical, Laterl, and Basement part.

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20
Q

Surface modifications

Types, Size, Location, and Function

A

Microvilli (GI tract) “striated border” , 1 um, absoroptin

Microvilli (Kidney) “bursh border”, 1 um, absorption

Stereocilia (Epididymis, DD, innear ear), 2um, absorption

Cilia (Respiratory, Oviduct), 10um, movement of stuff

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21
Q

What supports microvilli?

What is the purpose of microvilli?

Are microvilli pernament?

A

Actin

Increase surface area

Appear and disapear quickly

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22
Q

Stereocilia vs. Cilia

A

Cilia are larger and less dense

Stereocilia are smaller and more dense

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23
Q

Celiac sprue

A

Sensitivity to gluten (component of wheat flour)

Due to loss of microvilli in small intestine

= less absorption and osmotic diarrhea

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24
Q

Kartagener’s Syndrome

Immobile Cilia Syndrome

A

Dynein arms missing = cilia do not move

Chronic respiratory difficulty including bronchitis and sinusitis

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25
Q

Types of intermediate filaments

A

Keratin (epithelial cells)

Desmin (muscle cells)

Vimentin (fibroblast, endothelail, chondroblast, macrophage, mesenchymal)

Glial fibrillary acid protein (astrocytes)

Neurofilaments (neurons)

Lamins A, B, C (nuclear lamin of all cells)

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26
Q

Tunctional complex (terminal bar)

Other junctions?

A

Complex of structures

Zona occludens ZO (tight junction), belt-like, no cystoskeleton [functional]

Zona adherens ZA (adhesion belt), belt-like, actin - cadherin (CAMs) [mechanical]

Macula adherens MA (desmosome), spot, keratin - cadherin (CAMs) [mechanical]

Other

Gap Junctions GJ, spot, connexins forming connexons no cytoskeletom [functional]

Hemidesmosomes, spot, kerain - basement membrane [mechanical]

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27
Q

Basal Membrane subcomponents

What are these subcomponents are made of?

A

Basal lamina: lamina lucida (laminin, fibronectin, GAG) lamina densa (type IV collagen)

Reticular lamina (type IV and type VII collagen)

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28
Q

What is the shape of the basal membrane?

A

Infoldings with mitochondria

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29
Q

Basement Membrane types

A

Epithelium conntected to connective tissues (most common)

Epithelium connected to epithelium (aveoli of lung / glomerulus)

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30
Q

Serosa components

A

Mesothelium that lies on the connective tissue

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31
Q

Mucosa layers

A

Epithelium w/or w/o glands

Basement membrane

Lamina propia

Muscularis mucosae

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32
Q

Intestinal wall layers

A

Mucosa

Submucosa

Muscularis

Serosa

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33
Q

Exocrine gland by types of secretion

A

Serous (parotid, exocrine pancreas) = protein rich / carbhodyrate poor

Mucous (golbet cells) = carbohydrate rich / protein poor

Mixed (submandibular, sublingual) mix groups of cells

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34
Q

Exocrine glands

Secretory mechanisms

A

Merocrine (eccrine)

Apocrine

Holocrine

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35
Q

Most common gland mechanism?

A

Merocrine (sweat gland)

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36
Q

What layer are glands derived from?

A

Epithelium

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37
Q

What is the most common unicellular exocrine gland?

A

Goblet cell

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38
Q

What is the shape of the typical salivary exocrine gland?

A

Compound tubuloaveolar

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39
Q

Classification of connective tissue

A

Proper: loose, dense, adipose

Bone

Cartilage

Blood

Lymph

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40
Q

Three components of connective tissue

A

Ground bustance

Fibers

Cells

(GS + fibers = ECM)

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41
Q

Functions of connective tissue

A

Mechanical support

Protection of soft tissues

Physiological support (nerves, fluids, metabolites)

Storage (fat)

Immune defence

Repair of injuries

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42
Q

Composition of ground substance

Function of components

A

Gyclosaminoglycans (strongly hydrated = reistant to compression, negative charge = repulsive and slippery)

Proteoglycans (trap water, occupy space,

Glycoproteins (cell adhesions)

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43
Q

Functions of ground susbtance

A

Traps water (fullnes to skin, protection, reduces fluid loss, limits pathogenic invasion)

Anchors

Acts as a charge and size barrier (regulates access to cells)

Contributes to the physical properties of a connective tissue (reinforced concrete)

Regulates morphogenesis (migration, growth factor activation)

Facilitates cell migration

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44
Q

Which GAG is non-sulfated?

A

Hyaluronan

1 g can absorb 48 g of water

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45
Q

Distrubances of ground susbtance

A

Improper nutrient/waste management

Improper tissue development

Improper tissue growth

Cell malfunction: GAG accumulation in lysozomes (mucopolysaccharidoses)

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46
Q

Three types of fibers seen at the light microscope level

A

Reticular fibers (silver stain)

Elastic fibers (special stain)

Collagen (H&E)

* sometimes not seet because they are embeded in a ground susbtance

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47
Q

Types of collagen

A

Type I = stiff (bone, skin, tendon, dentin, fibrocartilage)

Type II = jelly (hyaline and elastic cartilage, viterous humor)

Type III = delicate (lymphatic tissue, adipose, liver, cardicascular, lung)

Type IV = filtration/support (basal lamina)

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48
Q

Diseases assocaited with collagen

A
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49
Q

Fibrillin

A

Family of proteins which provides the scaffolding for the deposition of the elastin core

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50
Q

Marfan syndrome cause

A

Mutation in fibrillin gene

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51
Q

Connecttive Tissue Cells

Fixed (resident) vs. Free (transient)

A

Fixed are derived from mesenchymal cell

Free are derived from hemopoetic cell

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52
Q

Pericytes

A

Stem cells for CT

Role in angiogenesis and hypercullar obsesity

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53
Q

Fibroblasts

A

Produce fibers and ground system

Found in embryonic, repaired, and traumatized tissues

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54
Q

Organization of elastic fibers

A

Fibers

Networks

Membrane

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55
Q

Plasma cells

A

Scattered in CT, but highly present in inflamation

Clock nucleus

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56
Q

Macrophages

A

Differentiate upon entry into the CT

Types: fixed and free

Part of the Mononuclear Phagoctic system (MPS)

APC

Phagocytosis may be immune or non-immune mediated

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57
Q

Mast cells

A

Possess granules containg histamine, heparin, and others considered to be primary mediators

Degranulate with the secondary exposure to an antigen (allergen)

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58
Q

Primary vs. Secondary response in Mast cells

A

Primary

IgE binding to Fc receptors

Secondary Response (in Color)

Antigen crosslinks IgE molecules
Granules released (primary mediators)
Secondary mediators released

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59
Q

White Fat cells

A

90% triglyceride

Storage, insulation, protection

Hormone production (leptin and adiponectin)

Number is determined perinatally

Cancers: Lipomas and Liposarcomas

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60
Q

Brown Fat cells

A

Many mitochondria

Specifc locations neck and inter-scapular regions of infant

Nerve are associated with brown fat (white fat does not have)

Thermogenesis by fatty acids oxidation

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61
Q

Classification of connective tissue

A

Loose connective tissue

Dense regular connective tissue

Densre irregular connective tissue

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62
Q

Cancer cells must have two heritable properites:

A
  1. Defiance of normal cell controls on division
  2. Invasion and colonization of foreign tissues
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63
Q

Karposi’s sarcoma

A

Malignant tumor of the connective tissue.

Often associated with AIDS

AIDS related Kaposi’s sarcoma is mediated by HIV, immune system suppression, and human herpesvirus-8 (HHV-8)

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64
Q

Philadephia chromosome

A

9-22 translocation

increases risk of developing CML (chronic myolegenous leukemia)

DNA break is always the same

Caricongenesis is linked with mutagenesis

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65
Q

Carcinogens that may cause mutations

A

Chemical (point mutations in DNA)

Ionazing radiation X-ray (cause translocation and breakage)

Transforming viruses (introduction of foreign DNA)

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66
Q

Relationship of exposure to carinogenesis

A

example of 2-naphtylamine

proportional to years of exposure

delayed onset

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67
Q

General steps in carcinogenesis

A

Mono layer propagation

Multi layer

Invasion

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68
Q

Characteristics of cancer cells

A
  1. Disregard cell proliferation internal and external signals
  2. Avoid apoptosis
  3. Circumvent limitations to proliferation (senesence, differentiation)
  4. Geneticall unstable (e.g. p53)
  5. Escape from their origin
  6. Survive and profilerate in foreign sites
  7. Mantained by cancer stem cells
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69
Q

Two classes of genes assocaited with carcenogenesis

A

Oncogenes (GOF)

Tumor Supressor (LOF)

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70
Q

Example of Tumor Suppresor

A
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71
Q

Example of Oncogene

A
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72
Q

BAD mechanism and inactivation

A
73
Q

Two types of signalling pathways

A

Pathway to drive cell cycle

Pathway to aquire nutriets

74
Q

Warburg effect

A

non-Hodking lymphoma NHL and fluorodeoxyglucose

High FDG uptake indicates cells with unusually active
glucose uptake and metabolism, a characteristic of tumors.

75
Q

Three categories of genetic alterations in cancers

A

Point mutations / deletion (e.g. Ras, EGF receptor)

Gene amplification (src, myc)

Chromosome Rearrangement (myc in Bukitt’s lymphoma or Abl in CML)

76
Q

p53

A

Tumor Suppressor

Transciption factor

p53 mutations found in 50% of cancers

77
Q

Gleevec

A

Specific inhibitor (prevent phsophorylation of Bcr-Abl-substrate complex

Prevent leukemia

78
Q

Iressa

A

Selective inhibitor of EGFR tyrosine kinease

Also called Her1 or ErbB-1

Effective against breast cancers

79
Q

Salirasib

A

Competitive inhibitor of ras binding to galectin

Ras mutations are found in 90% of all pancreatic cancers

80
Q

Zelboraf

A

targets the V600E mutation in Raf that constitutively activates Raf

Found in 1/2 of melanoma

81
Q

Cancer name derived from

A

Crab

Greek KARKINOS

crab-like extensions

82
Q

Properties of cancer

A

Uncontrolled Growth

Invasion and Metastasis

Clonal Dominance

Loss of Differentiation

83
Q

Benign. vs Malignant

A

Benign: unrestrained growth; circumscribed border; rarely kills

Malignant: unrestrained growth; invasion; metastais and kills host

84
Q

Definition of invasion

A

Active migration of neoplastic cells out of their tissue of origin and across host tissue boundaries

85
Q

Definition of metastasis

A

(1) A secondary tumor colony discontinuous from the primary tumor
(2) Arising from a tumor cell translocated from the primary tumor

86
Q

Definitions:

Tumor

Neoplasia

Oncology

Cancer

A

Tumor (swelling or mass) nonspecific suffic “_oma”

Neoplasia (new growth)

Oncology (Gr onkos = mass, bulk)

Cancer (crab; appearance vs. behavior)

87
Q

Metaplasia

A

A reversible histological event in which one adult cell type is changed into another adult cell type

88
Q

Atypia

A

A histological or cytological event non-conforming to an established type.

89
Q

Malignant vs. Benign type

Epithelium vs. Mesenchymal origin

Nomencalture

A

MESENCHYMAL

Benign “_oma” e.g. adenoma

**Malignant “_sarcoma” **e.g. liposarcoma

EPITHELIAL

Benign “_adenoma”

Malignant “_carcinoma” e.g. carcinoma

90
Q

Tumor additional descriptive terms

A

Papilloma

91
Q

Exceptions to cancer nomenclature

A

Non-benign: hepatoma, lymphoma, melanoma, mesothelioma, seminoma

Not neoplasm: hamartoma (disorganized overgrowth of normal tissue) choristoma (ectopic mass of non-neoplastic tissue abnormal for site)

Neoplasm of bone marrow origin “-emia” (e.g. leukemia)

Neoplasm of embryonic origin “-blastoma” (e.g. neuroblastoma)

92
Q

Events related to tumor progression

A

Changes

  1. Genetic (ONC, TS)
  2. Epigenetic
93
Q

Angiogenesis

A

Required for tumor progression 1 to 2 mm

Aid metastasis

94
Q

Size / Aggresivenes / Metastatis

A

The more aggressive cancers metastasize at smaller size.

95
Q

Benign vs. Malignant:

Uncontrolled proliferation

Monoclonality

Loss of differentiation

Genetic alterations

Angiogenesis

Invasion and metastasis

A
96
Q

Cancer therapy

A

Surgery

Radiotherapy

Chemotherapy

Immunotherapy

97
Q

Does the “invasion” as a trangression of the basement membrane apply to sarcomas?

A

No.

It is more difficult to determine invasion in sarcomas and distinguish sarcomas from benign mesenchymal tumors for that reason.

We must rely on other pathological findings like mitoses, proliferation index, size and necrosis.

98
Q

Multistep nature of tumor progression

A

Normal duct

Intraductal hyperplasia

Inraductal hyperplasia with atypia

Intraductal carinoma in situ

Invasive carcinoma

99
Q

Grading: 2 types

A

Tissue pattern: well, moderately, and poorly differentiated

Nuclear features: low, intermedaite, and high

I to IV

100
Q

Cancer staging

A

A measurment of degree of invasion and metastasis

Tumor Lymph Node Metastases (TNM), AJC

101
Q

Three routes for metastasis

A

Lymphatic (lymph nodes)

Hematogenous (lung, liver, brain, bone marrow and adrenals)

Transcoelomic spread (peritoneal, pleural, pericardial and subarachnoid spaces

102
Q

Metastasis route for carcinomas vs. Sarcomas

A

Carcinomas: lymph route

Sarcomas: blood

103
Q

Cancer heterogeneity

A

Mutant subclones are heterogeneous with respect to invasiveness, metastatic ablility, antigenicity and responsiveness to chemotherapy

104
Q

–Invasion and interaction with the extracellular matrix (ECM) is divided into 4 steps.

A
  1. Less cohesive (e-cadherins reduced)
  2. Attachement to matrix (laminin and fibronectin)
  3. Degradation (Metalloproteinases: collagenases and plasmin)
  4. Migrations (cytokines and cleavage products of ECM)
105
Q

Dissemination and Homing of cancer cells

A

Dissemination: Can circulate with leukocytes/platelets or alone

Homing: depends on vascular/lymphatic drainage, enhanced by adhesion molecules, proteases may inhibit

106
Q

Soild Seed Hypothesis of Paget

A
107
Q

Anatomical planes

A

Transverse plane (longitudinal axis)

Coronal/frontal plane (saggital axis)

Saggital plane (frontal axis)

Mid-saggital / Median plane

108
Q

Joints three types

A
  1. Synovial joint
  2. Fibrous joints
  3. Cartilaginous joints
109
Q

Synovial joint characteristics

A

Most common

Freely movable * not always

Lined by synovial membrane

Joint cavity opposed by articular cartilage (hyaline/fibrocaritlage)

Synovial membrane secretes synovial fluid

110
Q

Fibrous joint charactersitics

A

Held by fibrous tissue e.g. suture, intrerosseous membrane

Suture = fibrous joint

111
Q

Cartilaginous joint charactersitics

A

Held by cartilage e.g. epiphyseal plate and intervertebral discs (fibrocaritlage)

112
Q

Label structures in joints

A
  1. Periosteum
  2. Ligament
  3. Fibrous capsule
  4. Synovial membrane

3+4 = Articular capsule

  1. Compact bone
  2. Femur
  3. Join cavity (with synovial fluid)

8 Articular cartilage

  1. Synovial membrane
  2. Meniscus
  3. Tibia
  4. Infrapatellar fat pad
113
Q

Label epidermis

A
  1. Hair
  2. Afferent nerve ending
  3. Arrector muscle of hair
  4. Collagen and elastic fibers
  5. Sebaceous gland
  6. Hair follice
  7. Fat
  8. Cytaneous nerve
  9. Lymphatic vessel
  10. Superficial blood vessels
  11. Skin ligament (retinaculum cutis)
  12. Sweat gland
  13. Muscle
  14. Deep fascia
  15. Subcutaneous tissue (superficial facia)
  16. Dermis
  17. Epidermis
114
Q

What determines stiffness of skin

A

Skin ligaments

115
Q

Superficial Fascia characteristics

A

Fat

deep facia <-> Ligaments <-> dermis

Insulator

Protection for bony prominences

Blood vessels, nerves, and lymphatics

Glandular portion of sweat glands

116
Q

What separates muscle/bones?

A

Deep facia

Muscles / bones are in capsules

117
Q

Deep Fascia characterstics

A

Dense irregulat connective tissue

Attached by the ligaments to skin

Contacts muscle

Continuous with nerve

Connected to periosteum

Aids in moving the blood (muscle compartmentalization)

118
Q

Aponeurosis

A

Layers of flat broad tendons

119
Q

Thoraxs compnents

opened superiorly? opened inferiorly?

A

Ribs, sterum, cartilage, vertebra

Both open but diaphragm separates from abdominal cavity

120
Q

Is nipple a good measure of the position of T4? What about dermatome that originated from T4?

A

No. Yes.

121
Q

How far does respiration pushes diaphgram?

A

Deep expiration = 4th rib

Normal expiration = 6th rib

122
Q

Costodiaphragmatic recess

A

A potential space in the pleural cavity, at the posteriormost tips of the cavity, located at the junction of the costal pleura and diaphragmatic pleura.

The lungs expand into this recess during forced inspiration, however the recess never fills completely. During expiration, it contains no lung tissue, only pleural fluid.

123
Q

Heart location estimate

A

Between two joints of sternum body (around T4 and T9)

124
Q

Angle of Louie clinical application?

A

Heart sounds

125
Q

Is first rib palpable?

A

No

126
Q

Most fracured place in a rib?

A

Anterior to the angle

127
Q

Clinical importance of 2nd intercostal space

A

Intercostal brachial nerve = pain in upper limb in case of heart attack

128
Q

What is facet?

A

Smooth surface that allows articulation

129
Q

Surface landmarks (lines)

A

Scapular (midclavicular) line

Sternal line

Posterior/Mid/Anterior axillary line

130
Q

Pectus Excavatum

A

Rapid growth of cartilage that pushes the sternum backwards. Is surgically repairable.

131
Q

Costochondritis

A

Pain at the junction of the costal cartilage with the sternum. This pain is generally reproducible by pressure on the location.

You can reproduce this pain by pushing, but you cannot reproduce the pain caused by heart attack.

132
Q

Deep fascia synonym

A

Investing fascia

133
Q

Location of the breast

A

Between the 2nd and 6th ribs

From the lateral border of sternum to midaxillary line

Separated by retromammary space between deep (investing facia) from pectoralis major

134
Q

Suspensory ligament synomyms

A

Cooper’s ligament

Retinacula cutis

135
Q

What is the breast size determined by in non-lactating breast?

A

The amount of fat surrounding the glandular tissue

136
Q

When does the glandular tissue in breast develop?

A

Puberty

Fat deposition occurs

Lactiferous ducts give rise to 15-20 lobes of glandular tissue. These lobes further divide into lobules.

137
Q

How many lobes drain into a duct?

How many ducts drain into a sinus?

A

15-20

12-15

138
Q

Does the mechanism sucking (low pressure) releases milk?

A

No. The response releases the milk accumulated in sinuses.

139
Q

Direction of the lymph originating from breast

A

To the other breast

To parasternal nodes

Down to the liver

To interpectoral nodes

To posterior axillary (subscapular) nodes (most likely)

140
Q

Sentinel nodes

A

The first draining node

141
Q

Which nodes are sentinel nodes for the breast?

A

Axillary

Interpectoral

142
Q

Right versus Left side Lymph Drainage

A

One thoracic duct (left) dumps to left subclavian

Right lymphatic duct empties to equivalent two structures on right side

143
Q

Polythelia

A

Multiple nipples

144
Q

Location of breast augumentation

A

old : subglandular

new : submuscular

145
Q

Gynecomastia

A

is the growth of abnormally large breasts in males.

146
Q

Where does the neurovascular bunlde lines in ribs?

A

Between two deepest layers:

Innermost intercostal muscle

Internal intercostal muscle

147
Q

Why intercostal veins do not go to vena cava?

A

There is no vena cava around heart

148
Q

Accessory respiratory muscle

A

Any muscle attaching to the ribs or sternum has the potential to act as an accessory respiratory muscle by either elevating or depressing the ribs.

pectoralis major and minor, the scalenes, the serratus posterior and serratus anterior and the levator costarum

abdominal in forced respiration

149
Q

Values for the skin

A

Skin is the largest organ of the body

8-10 pound

  1. 6-2 m2
  2. 5-4mm thickness 0.5 eye lids 4mm palms
150
Q

Tension lines (langer lines)

A

The dermis contains a dense network of interlacing collagen and elastic fibers. These fibers provide skin tone and account for the strength and toughness of the skin. The predominant pattern and direction of the fibers determines the characteristic tension and wrinkle lines in the skin.

Elastic fibers deteriorate with age.

151
Q

Breast metastases destination

A

Bone 80% (osteolytic metastases associated with hypercalcemia, bone pain, and fractures)

CSN particullary brain 20%

152
Q

Herpes Zoster (Shingles)

A

An inflammatory skin disease caused by

Herpes simplex virus or varicella-zoster (chickenpox) virus (VZV).

It produces painful eruptions of groups of deep-seated vesicles

Herpes zoster is primarily a viral disease of the spinal ganglia (dorsal root ganglia). It is primarily a sensory neuropathy, although (in rare cases) muscular weakness can also occur.

153
Q

What is the major cause of cell death?

A

Programmed cell death

154
Q

Necrosis vs. Apoptosis

A

Cell size: swelling / shrinkage

Nucleus: disintegrate / chromatin condensation and fragmentation

Plasma membrane: distrupted / intact

Cellular content: enzymatic digestion / intact

adjacent inflammation: frequent / no (phagocytosis)

155
Q

Eat me signals on cell surface for

engulfemt and phagocytsis

A

Flipped-out phosphatidylserine

Thrombospondin

Adhesive glycoprotein

Natural antibodies, and proteins of complement system, notably C1q

Soluble factors

156
Q

Does phagocytosis cause inflammation?

A

No

157
Q

Initiation of apoptosis 2 pathways

A

Mitochondrial pathway (intrinsic signals)

Death receptor–initiated pathway (extrinsic signals)

158
Q

What executes apoptosis?

A

Caspase cascade

159
Q

Caspase

name?

A

Caspase: cysteine-aspartic proteases

Possesses cysteine residue in active site

Caspase cleaves following aspartate residue in target peptide

Nearly 100 different cell target proteins (nuclar lamins, acin, myosin, golgi matrix proteins)

160
Q

Apoptotic caspases

Initiatior

Executioner

A

Initiatior: 2,8, 9, 10

Executioner 3, 6, 7

161
Q

Mitochondrial (intrinsic) pathway

A

Bcl-2 family act at the mitochondria

Cytochrome c released from mitochondria triggers caspase activation

162
Q

Intrinsic pathway: release of cytochrome C

A
163
Q

Blc2 family examples

A

(regulator) anti-apoptotic Bcl2 protein: Bcl2, Bcl-X

(effector/channel) pro-apoptotic: Bak, Bax

(sensor) pro-apoptotic: Bad, Bim, Bid, Puma, Nox

164
Q

What domain mediates binding between proapoptotic and antiapoptotic protein forming heterodimers?

A

BH3

165
Q

Intrinsic pathway: controlling mitochonrial release of anti-IAP

A

Caspases are also regulated by the IAP (inhibitor of apoptosis) to prevent spontaneously cleaved caspases

Triggers apoptosome assembly that activates caspase cascade

166
Q

Apoptosome assembly

A

Cytochrome c binds Apaf1 (apoptosis-activating factor-1), causing it to hydrolyze its bound dATP-dADP

replacement of the dADP with dATP -> aggregation

Heptameric apoptosome

Recruits procaspase-9 through caspase recruitment domain (CARD) on each protein

Caspase cascade

167
Q

p53 mediates apoptosis

A

When DNA damage is too extensive to repair, ataxia telangiectasia mutated (ATM) and Chk2 protein kinases phosphorylate/activate p53 tumor suppressor protein

  • > Cdk inhibitor p21, which inhibits Cdk2/cyclin E complexes, halting cell cycle progression in G1 (cell cycle arrest).
  • > BH3-only proteins PUMA and Noxa, which activate BH123 proteins Bax and Bak, leading to mitochondrial release of cytochrome c and activation of caspase-9 (apoptosis).

Mediates both cell cycle arrest and apoptosis

168
Q

Extrinsic death receptor

A

Death ligands: Tumor necrosis factor (TNF) family of signal proteins (Fas ligand).

Death receptors: TNF family receptors (Fas receptor).

These receptors directly activate a distinct initiator caspases, caspase-8 and/or -10.

169
Q

Extrinsic or death receptor initiated pathway

A

Killer T cell-induced apoptosis via Fas death receptor

TNF and other cell death receptor ligands consist of three polypeptide chains, so their binding to cell death receptors induces receptor trimerization.

FADD + proscaspase = DISC

Caspase-8 is recruited to the receptor and activated via interaction with adaptor molecules. Once activated, caspase-8 cleaves and activates effector caspases (the extrinsic pathway of apoptosis).

In addition, caspase-8 cleaves the BH3-only protein Bid, which activates the intrinsic pathway of apoptosis, leading to caspase-9 activation.

170
Q

How cells are renewed?

A

Most differentiated cells are are no longer able to proliferate. Following injury, these cells are replaced by self-renewing stem cells.

Some differentiated cells that are arrested in G0 stage of the cell cycle retain the ability to resume proliferation as needed

171
Q

Examples of cells proliferating

A

1) **Vascular Endothelial Growth Factor VEGF **(released by tissue deprived of oxygen and acting on endothelial cells)
2) Epithelial cells (after liver removed during surgery)
3) Platelet Derived Growth Factor PDGF (cut wound)

172
Q

What is hyperplasia/hypertrophy?

A

dedifferentiation and growth

173
Q

Assymetric divison

A

stem cells produce one daughter cell that remains continues proliferating indefinitely, and one progenitor cell that further divides and terminally differentiates.

blood cells, sperm, epithelial cells of skin, liver, and lining digestive tract, skeletal muscle myosatellite cells, neural stem cells, and cardiac stem cells.

174
Q

Renewal of the intestinal epithelium

A

Intestinal epithelial cells are exposed to harsh environment and live only a few days before they die by apoptosis

These cells are replaced by slowly-dividing stem cells in the intestinal crypts

Stem cells give rise to a population of transit-amplifying cells, which proliferate for 3-4 divisions and then differentiate into the three types of the colon surface epithelium (absorptive epithelial cells and two secretory cells, called goblet cells and enteroendocrine cells).

175
Q

Adult stem cells therapy

A

ex. hematopoietic stem cells / skin epithelial stem cells

Advantage: eleminates potential complication of graft rejection

Disadvantage: technical problems, not all tissue types, lack of pluripotency

176
Q

Embryonic stem cells

A

Derived from the inner cell mass of blastocyst

Advantages: ES pure stem cell; pluripotent; successful clinical transplanation

Disadvantage: cell culture conditions to obstain specific tissue; ethics

177
Q

Somatic cell nuclear transfer vs. Therapeutic cloning

A

Somatic cell nuclear transfer (dolly; injecting nucleus into the egg)

Therapeutic cloning (growin organs; injecting nucles to the egg of the same person)

178
Q

Induced pluripotent stem (iPS) cells

A

iPS cells: pluripotent stem cells artificially derived from a non-pluripotent cell - typically an adult somatic cell - by inducing a “forced” expression of specific genes.

Advantages: pluripotency; no tissue rejection; research

Disadvatage: technique not established; causing cancers

179
Q

Too much vs. too little apoptosis

A

Too little: Cancers, autoimmune, hematological diseases

Too much: neurodegenrative diseases; infection; ischemia; autoimme disease

Block 1 (25 decks)

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